This project aims to create a new class of semiconducting polymers for applications in wearable and implantable healthcare that-in contrast to all other research on electronic skin-will actually have properties inspired by biological tissue: extreme elasticity, biodegradability, and the ability to self-heal. The goal of organic bioelectronics is to detect and treat disease by using signal transducers based on organic conductors and semiconductors in wearable and implantable devices. Except for the carbon framework of these otherwise versatile materials, they have essentially no properties in common with biological tissue: electronic polymers are typically stiff and brittle, and do not degrade under physiological conditions. Seamless integration with soft, biodegradable, and self-healing tissue has thus not yet been realized. In Phase I of this project, we will develop a modular synthetic methodology based on segmented polymerization of semiconducting segments and biodegradable elastomeric segments. Phase II will characterize the properties of this new class of materials, which will be the first polymeric semiconductors to have the mechanical properties of human tissue, the first known semiconductors capable of self-repair, and the first organic semiconductors that can degrade under physiological conditions into biocompatible byproducts, which will be established in a rat model. Phase III will use the synthetic materials as transducers of chemical, biomolecular, mechanical, and electrical signals in several modalities as proof-of-concept devices, including skin-like pressure sensors for instrumented prostheses, biochemical sensors for wearable health monitors, and photodetectors for artificial retinas. Phase III will culminate in the demonstration of an implantable epidural pressure sensor for continuous monitoring of intracranial pressure (ICP). The long-term goal of this research is to endow these devices with the capability of wireless power and telemetry. The strength of the proposal is its vertically integrated strategy that combines molecular engineering and synthetic chemistry with determination of biodegradability and biocompatibility, the fabrication of devices, and their use in detecting physiological signals relevant to a range of diseases. The proposed research will build on my documented experience executing and directing projects in an especially broad range of topics: total synthesis of medicinally active compounds, micro- and nanofabrication of electronic devices, and development of stretchable materials and skin-like sensors for applications in implantable health monitoring. I coined the term Molecularly Stretchable Electronics to describe the research of my group, which is becoming internationally recognized as a leader in the mechanical properties of functional electronic polymers. The NIH Director's New Innovator Award would jumpstart my group's progress toward the long-term goal of my research: designing soft electronic materials specifically for applications in the health sciences.